1. Field of the Invention
The present invention relates to inducible antimicrobial and antifungal peptides of the mammalian epithelial tissue. In particular, the present invention relates to a mammalian epithelial peptide designated lingual antimicrobial peptide (LAP) and to its precursor peptides. The invention present invention also relates to cDNA segments encoding LAP and its precursor peptides, and to methods of treating microbial infection of the epithelium.
2. Description of the Prior Art
Epithelium is a complex tissue responsible for forming an initial, physical barrier protecting the body against potentially harmful environments. Epithelial tissue covers the outer body surfaces and lines the luminal surface of the respiratory tract, the gastrointestinal tract, and the genitourinary system to protect these surfaces from exposure to the outside environment. Epithelial surfaces, therefore, serve a "defensive" function, protecting the host from the environment (Jacob and Zasloff, Ciba Foundation Symposium 186, 1994).
Antimicrobial peptides provide a second, chemical line of defense supplementing the physical barrier of the epithelial tissue surfaces. Antimicrobial peptides, produced by various tissues in the body, have antibacterial, antifungal, and antiviral activity. These peptides, which can be classified into several families, have been found in a variety of tissues from diverse species. For example, magainins have been isolated from frogs (Zasloff, M., Proc. Natl. Acad. Sci. USA 84: 5449-5453, 1987) and cecropins have been found in insects (Boman, H. G., Cell 65: 205-207, 1991). In addition, two groups of peptides within the defensin family have been identified. .beta.-defensins have been isolated from neutrophils of cows (Selsted et al., J. of Biol. Chem. 268: 6641-6648, 1993) and from tracheal mucosa of cows (Diamond et al., Proc. Natl. Acad. Sci. USA 88: 3952-3956, 1991; and Diamond et al., Proc. Natl. Acad. Sci. USA 90: 4596-4600, 1993), while .alpha.-defensins have been isolated from neutrophils of humans (Lehrer et al., Annual Rev. Immunol. 11: 105-128, 1993) and from the epithelial-derived Paneth cells at the base of the crypts of the small intestine in murine and human GT tracts (Ouellette et al., J. Cell Biol. 108: 1687-1695, 1989; and Jones and Bevins, J. Biol. Chem. 267: 23215-23225, 1992). The antimicrobial peptides provide a second line of defense, killing bacteria and fungus pathogens which penetrate the physical barrier.
One example of epithelial tissue is the mammalian tongue which is covered by a dense stratified epithelium. The tongue is in an environment constantly exposed to various microorganisms that are part of the microbial flora of the mouth. Despite is constant exposure to microbials, invasive infections of the tongue rarely ensue even when abrasions occur on the tongue's surface. In investigating the infection resistance property of the mammalian tongue, a novel antibacterial and antifungal peptide was isolated from the extracts of bovine tongue epithelial tissue.